Outcomes Of Serious Infections Research Articles

Epidemiology, Time Trends, and Outcomes of Serious Infections in Patients With Vasculitis: A Nineteen-Year National Study.

To examine the epidemiology, time trends, and outcomes and types of serious infections in people with vasculitis in the US. We identified people with vasculitis who were hospitalized with a primary diagnosis of pneumonia, sepsis/bacteremia, urinary tract infection (UTI), skin and soft tissue infections, or opportunistic infections in the 1998-2016 US National Inpatient Sample. We used adjusted logistic regression to examine the predictors of a hospital stay >3 days, total hospital charges greater than the median, discharge to a non-home setting, and in-hospital mortality. We noted 111,345 serious infections in patients with vasculitis (14% of all vasculitis hospitalizations). Among the patients, the mean age was 67.3 years, the Deyo-Charlson comorbidity index score was ≥2 in 54%, 37% were male, and 67% were White. The serious infection hospitalization rate per 100,000 US National Inpatient Sample claims in 1998-2000 versus 2015-2016 (and rates of increase) in patients with vasculitis was as follows: overall, 12.14 versus 25.15 (2.1-fold); opportunistic infections, 0.78 versus 0.83 (1.1-fold); skin and soft tissue infections, 1.38 versus 2.52 (1.8-fold); UTI, 0.35 versus 1.48 (4.2-fold); pneumonia, 7.10 versus 6.23 (0.9-fold); and sepsis, 2.53 versus 14.10 (5.6-fold). Pneumonia was the most common serious infection in 1998-2000 (58%) versus sepsis in 2015-2016 (56%). Sepsis, older age, Deyo-Charlson comorbidity index score of ≥2, urban hospital, or medium/large hospital (by number of beds) were associated with higher health care utilization and in-hospital mortality rates; Northeast region and Medicare and Medicaid payer type were associated with higher rates of health care utilization. Serious infection hospitalization rates are increasing in patients with vasculitis except among those with pneumonia. Sepsis was the most common serious infection in 2015-2016. Several patient and hospital factors are associated with health care utilization and mortality in serious infection hospitalization in vasculitis.

Hospitalized Infections in People With Osteoarthritis: A National US Study.

To study the incidence, time trends, and outcomes of serious infections in people with osteoarthritis (OA). We used 1998-2016 US National Inpatient Sample (NIS) data. Using recommended weights, we examined the epidemiology of 5 types of serious infections requiring hospitalization in people with OA (opportunistic infections [OIs], skin and soft tissue infections [SSTIs], urinary tract infections [UTIs], pneumonia, and sepsis/bacteremia). We performed multivariable-adjusted logistic regression analyses to analyze factors associated with healthcare utilization (hospital charges, length of hospital stay, discharge to nonhome setting), and in-hospital mortality. Of all serious infection hospitalizations, 46,708,154 were without OA and 3,258,416 had OA. People with OA were 16.4 years older, more likely to be female (52% vs 65%), White (59% vs 70%), have a Deyo-Charlson Comorbidity Index (DCCI) ≥ 2 (42% vs 51%), receive Medicare (54% vs 80%), and less likely to receive care at an urban teaching hospital (45% vs 39%). Serious infection rates per 100,000 NIS hospitalizations increased from the study period of 1998-2000 to 2015-2016: OI (from 4.5 to 7.2); SSTI (from 48.4 to 145.9); UTI (from 8.4 to 104.6); pneumonia (from 164.0 to 224.3); and sepsis (from 39.4 to 436.3). In multivariable-adjusted analyses, older age, higher DCCI, sepsis, northeast region, urban hospital, and medium or large hospital bed size were significantly associated with higher healthcare utilization outcomes and in-hospital mortality; Medicaid insurance, non-White race, and female sex were significantly associated with higher healthcare utilization. Serious infection rates have increased in people with OA. Association of demographic, clinic, and hospital variables with serious infection outcomes identifies potential targets for future interventions.

Serious infections in people with systemic sclerosis: a national US study

ObjectiveTo study incidence, time trends, and outcomes of serious infections in systemic sclerosis (SSc).MethodsWe used the 1998–2016 US National Inpatient Sample data. We examined the epidemiology, time trends, and outcomes of five serious infections (opportunistic infections (OI), skin and soft tissue infections (SSTI), urinary tract infection (UTI), pneumonia, and sepsis/bacteremia) in hospitalized people with SSc. We performed multivariable-adjusted logistic regression analyses to analyze independent association of factors with healthcare utilization (hospital charges, length of hospital stay, discharge to non-home setting) and in-hospital mortality.ResultsThere were 49,904,955 hospitalizations with serious infections in people without SSc and 61,615 in those with SSc. During 1998–2016, the most common serious infections in SSc were pneumonia (45%), sepsis (32%), SSTI (19%), UTI (3%), and OI (3%). In 2013–2014, sepsis surpassed pneumonia as the most common serious infection; by 2015–2016, sepsis was 1.8 times more common than pneumonia. Over the study period, hospital charges increased, while length of hospital stay and in-hospital mortality decreased, overall and for each serious infection. Multivariable-adjusted analyses showed that sepsis, age ≥ 80 years, and Deyo-Charlson score ≥ 2 were associated with significantly higher odds of healthcare utilization and in-hospital mortality, and Medicare or Medicaid insurance payer, Northeast location, urban teaching or non-teaching hospital, and medium or large hospital bed size with significantly higher odds of healthcare utilization.ConclusionsOutcomes in people with SSc hospitalized with serious infections have improved over time, except higher hospital charges. Identification of factors associated with higher healthcare utilization and in-hospital mortality allows for developing interventions to improve outcomes.

Serious infections in people with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA): a time-trend national US study.

To assess incidence, time-trends, and outcomes of serious infections in people with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA). We examined the 1998-2016 US National Inpatient Sample for serious infections in PMR or GCA, namely, opportunistic infections (OI), skin and soft tissue infections (SSTI), urinary tract infection (UTI), pneumonia, and sepsis/bacteremia. Multivariable-adjusted logistic regressions assessed association of the type of infection, demographics, comorbidity, and hospital characteristics with healthcare utilization and mortality. Hospitalized with serious infections, those with PMR or GCA were 2 decades older than people without PMR or GCA, and more likely to be female or white or have higher Deyo-Charlson index score or higher income. Sepsis rates in the general population, PMR, and GCA cohorts were 10.2%, 17.7%, and 18.9% in 2015-2016, respectively. Incidence rates of serious infections/100,000 NIS claims in PMR and GCA in 2015-2016 were as follows (rounded off): OI, < 1 and < 1; SSTI, 4 and 1; UTI, 4 and 1; pneumonia, 9 and 2; and sepsis, 20 and 4, respectively. Sepsis surpassed pneumonia as the most common serious infection in 2011-2012. In multivariable-adjusted analyses in the PMR cohort, sepsis, female sex, Deyo-Charlson comorbidity score ≥ 2, Medicare or Medicaid insurance, urban hospital location, and large hospital bed size were associated with significantly higher healthcare utilization and/or in-hospital mortality. Similar associations were noted in the GCA cohort. Incidence of serious infections, especially sepsis, increased in both PMR and GCA cohorts over time. Interventions to improve serious infection outcomes in PMR/GCA are needed. Key Points • PMR/GCA patients with hospitalizedserious infections were 2 decades older than the general population. • Sepsis surpassed pneumonia as the commonest hospitalizedserious infection in PMR/GCA in 2011-2012. • Sepsis, female sex, comorbidity, Medicare/Medicaid insurance, and urban location were associated with higher healthcare utilization and in-hospital mortality.

Resistance and heteroresistance to colistin among clinical isolates of Acinetobacter baumannii.

Colistin is one of the most effective alternatives for treating Acinetobacter baumannii infections. The aim of this study was to determine colistin resistance and heteroresistance rates in A. baumannii from clinical samples in Hacettepe University clinical microbiology laboratory between June 2016 and January 2017. A total of 200 isolates were included in the study. In vitro susceptibility to amikacin, gentamicin, ceftazidime, piperacillin/tazobactam, meropenem, ciprofloxacin, and tigecycline were determined by disk diffusion test. Most isolates were multiresistant as they exhibited resistance to aminoglycosides, β-lactams, and fluoroquinolones. Colistin susceptibility was determined by broth microdilution (BMD) test (EUCAST standards) and was compared with E-test (bioMérieux, France) in 120 isolates. In 14 blood isolates that were susceptible to colistin (MIC ≤ 2mg/L), heteroresistance was investigated with the population analysis profile (PAP) method. Overall resistance (n = 200) to colistin was 28% by BMD. Among the 120 isolates where the two tests were compared, resistance to colistin was 25.8% versus 4.2% with BMD and E-test, respectively. Three blood isolates (21.4%) were heteroresistant to colistin. With E-test, a majority of the resistant isolates are overlooked and in vitro susceptibility to colistin should be determined with broth dilution method. This is the first study in Turkey reporting heteroresistance in A. baumannii isolates by the PAP method and emphasizes the need to test for heteroresistance in relation to clinical outcome in serious infections due to A. baumannii.

Serious infections among unselected patients with ST-elevation myocardial infarction treated with contemporary primary percutaneous coronary intervention

Contemporary studies assessing the frequency, characteristics, and outcomes of serious infections (SIs) in patients presenting a ST-elevation myocardial infarction are scarce. Prospective cohort of consecutive patients undergoing primary percutaneous coronary intervention (pPCI). Serious infection was defined as the presence of infection that prolonged hospitalization. Community-acquired infection (CAI) was defined by SI diagnosed in the first 72 hours of hospitalization, whereas hospital-acquired infections (HAI) were those diagnosed after 72 hours of hospital admission. From December 2009 to November 2012, 1,486 patients were included in the analysis. Serious infection was present in 58 (3.9%) individuals; 30 (2%) patients had CAI and 28 (1.9%) patients had HAI. Respiratory tract infection was responsible for 82% of the SI. Patients with SI were older, had more comorbidities, and had worse angiographic results of the pPCI procedure when compared with those without SIs. After multivariable adjustment, SI was associated with an approximately 10-fold risk of 30-day death. Patients with CAI had more often a history of smoking, Killip III/IV on hospital admission, worse pPCI, and angiographic results than did patients with HAI. However, no differences were seen in 30-day major cardiovascular outcomes between patients with CAI and HAI. In a contemporary cohort of unselected ST-elevation myocardial infarction patients representative of the daily practice, SI was uncommon but associated with worse pPCI results and high risk of mortality. The occurrences of CAI or HAI were similar, but CAI patients presented distinctly worse angiographic outcomes than did patients with HAI.

Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis

ObjectiveThis observational cohort study investigated the impact of biological (b) disease-modifying antirheumatic drugs (DMARDs) on the outcomes of serious infections (SIs) in patients with rheumatoid arthritis.MethodsWe investigated outcomes of SIs...

Infection risk in patients with rheumatoid arthritis treated with etanercept or adalimumab

ObjectivesTo compare the risk of infection for rheumatoid arthritis (RA) patients who took etanercept or adalimumab medication in a nationwide population. MethodsRA patients who took etanercept or adalimumab were identified in the Taiwan's National Health Insurance Research Database. The composite outcome of serious infections, including hospitalization for infection, reception of an antimicrobial injection, and tuberculosis were followed for 365 days. A Kaplan–Meier survival curve with a log-rank test and Cox proportional hazards regression were used to compare risks of infection between the two cohorts of tumor necrosis factor (TNF)-α antagonists users. Hazard ratios (HRs) were obtained and adjusted with propensity scores and clinical factors. Sensitivity analyses and subgroup analyses were also performed. ResultsIn total, 1660 incident etanercept users and 484 incident adalimumab users were eligible for the analysis. The unadjusted HR for infection of the etanercept users was significantly higher than that of the adalimumab users (HR: 1.93; 95% confidence interval (CI): 1.09–3.42; p=0.024). The HRs were 2.04 (95% CI: 1.14–3.65; p=0.016) and 2.02 (95% CI: 1.13–3.61; p=0.018) after adjusting for propensity scores and for propensity scores in addition to clinical factors, respectively. The subgroup analyses revealed that HRs for composite infection was significantly higher in patient subgroups of older age, female, as well as patients who did not have DM, COPD, and hospitalization history at the baseline. ConclusionIn this head-to-head cohort study involving a nationwide population of patients with RA, etanercept users demonstrated a higher risk of infection than adalimumab users. Results of this study suggest the possible existence of an intra-class difference in infection risk among TNF-α antagonists.

Evolution of tigecycline resistance inKlebsiella pneumoniaein a single patient

Carbapenemase-producing Klebsiella pneumoniae infections carry serious clinical and infection-control implications. Isolates possessing such hydrolyzing enzymes have been described in the United States and around the world. Besides being resistant to carbapenems, they usually confer resistance to fluoroquinolones, piperacillin-tazobactam, and extended-spectrum cephalosporins. Tigecycline demonstrates in vitro activity against these organisms, but reported resistance raises concern about tigecycline use for these infections. We describe a carbapenemase-producing K pneumoniae evolving resistance to tigecycline in a 75-year-old male after a prolonged stay in a critical care unit.

Clinical outcome of empiric antimicrobial therapy of bacteremia due to extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae

BackgroundPrompt administration of adequate empiric antimicrobial therapy is a major determinant influencing the outcome of serious infections. The objective of this study was to describe empiric antimicrobial therapy employed and assess its effect on the outcome of patients bacteremic with extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae.FindingsA retrospective surveillance study of all patients with bacteremias caused by ESBL-producing E. coli and K. pneumoniae (EK-ESBL) from 2000-2007 in the Calgary Health Region was conducted. Data were available for 79 episodes of bacteremia among 76 patients. Forty-four (56%) were male, the median age was 70.0 yrs [interquartile range (IQR) 60.6-70.1 yrs], and 72 (91%) episodes were E. coli. Seventy-four episodes (94%) were treated with empiric therapy within the first 48 hours. A non-statistically significant increased mortality occurred in those treated empirically with a beta-lactam/beta-lactamase inhibitor combination (6/16; 38% vs. 10/53; 18%; p = 0.063) while empiric carbapenem therapy was associated with lower mortality (0/10 died vs. 16/53 (30%), p = 0.089). Only 42 (53%) episodes received adequate therapy within the first 48 hours. The median time to first adequate antibiotic therapy was 41.0 hours [IQR 5.8-59.5] (n = 75). The case-fatality rate was not different among those that received adequate compared to inadequate therapy by 48 hours as compared to inadequate empiric therapy (9/42; 21% vs. 7/37; 19%; p = 1.0).ConclusionInadequate empiric therapy is common among patients with EK-ESBL bacteremia in our region but was not associated with adverse mortality outcome.

Clinical and Microbiological Outcomes of Serious Infections with Multidrug-Resistant Gram-Negative Organisms Treated with Tigecycline

Eighteen patients received tigecycline as treatment for infection due to multidrug-resistant gram-negative bacilli, including Acinetobacter baumannii and Klebsiella pneumoniae carbapenemase- and extended-spectrum beta-lactamase-producing Enterobacteriaceae. Pretherapy minimum inhibitory concentration values for tigecycline predicted clinical success. Observed evolution of resistance during therapy raises concern about routine use of tigecycline in treatment of such infections when other therapies are available.

Association of human leukocyte antigen with outcomes of infectious diseases: the streptococcal experience.

The role of host genetic factors in determining susceptibility to infections has become more evident. Certain individuals appear to be predisposed to certain infections, whereas others are protected. By studying the immune response and the genetic makeup of susceptible and resistant individuals a better understanding of the disease process can be achieved. Infections caused by group A streptococci offer an excellent model to study host-pathogen interactions and how the host genetic variation can influence the infection outcome. These studies showed that the same clone of these bacteria can cause severe or non-severe invasive disease. This difference was largely related to the human leukocyte antigen class 11 type of the patient. Certain class II haplotypes present the streptococcal superantigens in a way that results in responses, whereas others present the same superantigens in a way that elicits very potent inflammatory responses that can lead to organ failure and shock. These findings underscore the role of host genetic factors in determining the outcome of serious infections and warrants further investigations into how the same or different genetic factors affect susceptibility to other emerging and re-emerging pathogens.

Ciprofloxacin in polyethylene glycol-coated liposomes: efficacy in rat models of acute or chronic Pseudomonas aeruginosa infection.

In a previous study in experimental Klebsiella pneumoniae pneumonia, the therapeutic potential of ciprofloxacin was significantly improved by encapsulation in polyethylene glycol-coated ("pegylated") long-circulating (STEALTH) liposomes. Pegylated liposomal ciprofloxacin in high doses was nontoxic and resulted in relatively high and sustained ciprofloxacin concentrations in blood and tissues, and hence an increase in the area under the plasma concentration-time curve (AUC). These data correspond to data from animal and clinical studies showing that for fluoroquinolones the AUC/MIC ratio is associated with favorable outcome in serious infections. Clinical failures and the development of resistance are observed for marginally susceptible organisms like Pseudomonas aeruginosa and for which sufficient AUC/MIC ratios cannot be achieved. In the present study the therapeutic efficacy of pegylated liposomal ciprofloxacin was investigated in two rat models of Pseudomonas aeruginosa pneumonia. In the acute model pneumonia developed progressively, resulting in a rapid onset of septicemia and a high mortality rate. Ciprofloxacin twice daily for 7 days was not effective at doses at or below the maximum tolerated dose (MTD). However, pegylated liposomal ciprofloxacin either at high dosage or given at low dosage in combination with free ciprofloxacin on the first day of treatment was fully effective (100% survival). Obviously, prolonged concentrations of ciprofloxacin in blood prevented death of the animals due to early-stage septicemia in this acute infection. However, bacterial eradication from the left lung was not effected. In the chronic model, pneumonia was characterized by bacterial persistence in the lung without bacteremia, and no signs of morbidity or mortality were observed. Ciprofloxacin administered for 7 days at the MTD twice daily resulted in killing of more than 99% of bacteria in the lung; this result can also be achieved with pegylated liposomal ciprofloxacin given once daily. Complete bacterial eradication is never observed.

INCIDENCE OF INFECTIONS IN CADAVER KIDNEY RECIPIENTS TREATED WITH NEORAL, CELLCEPT, AND PREDNISONE

731 Infection is one of the major causes of patient death in kidney transplant recipients. The purpose of this study was to evaluate the effect of Neoral, Cellcept, and Prednisone (group A) on the incidence and outcome of serious infections requiring hospitalization compared to Neoral, Imuran, and Prednisone immunosuppression (group B). 103 consecutive Neoral treated cadaver kidney recipients transplanted between January 1994 and December 1996 were analyzed. OKT3 or ATGAM was used for induction therapy in all recipients. 47 recipients were in Group A and 56 in Group B. The daily dose of Cellcept was 1 to 3 gms in group A and Imuran 1mg/kg body weight in Group B. Cyclosporine blood levels were maintained around 300ng/ml. Acute rejections were treated initially by steroids and steroid resistant rejections were treated with OKT3. 10 recipients (21%) in group A and 26 (46%) in Group B were treated for rejection.(P=0.01) In group A, 22 recipients (46%) developed serious infections of which 8 were CMV, and 14 bacterial. In group B, 10 recipients(17%) developed serious infections, 8 due to bacterial sepsis, one each due to CMV and varicella zoster. The differences between the 2 groups with regard to incidence of overall infections (P=0.01) and CMV infections(P=0.005) were statistically significant. 6 recipients in group A (60%) and 6 in group B(23%) with rejection developed infections within 100 days of treatment of rejections. In the 22 recipients that developed infection in group A the daily dose of Cellcept was 1gm in 4 recipients (18%), 2 gms in 10(46%) and 3 gms in 8(36%). In 8 recipients with CMV infection in group A, the daily dose of Cellcept was 2gms in 5 recipients(62%) and 3gms in 3 recipients(38%). 27% of recipients with infection in group A and 60% in group B had been treated for acute rejection. Patient survival was 97%, 93% & 91% in group A and 96%, 93% and 86% in Group B at 1,2, and 3 years respectively.(P=NS) 3 recipients(6%) in Group A and 5(9%) in Group B died of infection. Graft survival was 97%, 91%, and 89% in Group A and 82%, 69% and 64% in Group B at similar intervals (P=0.02). In group A, patient death due to infection was the major cause of graft loss. We conclude that in Group A the incidence of overall infection and CMV infection is significantly greater compared to group B. In group A higher i ncidence of infection did not correlate to the higher dose of Cellcept. While Neoral, Cellcept, and Prednisone combination is superior to Neoral, Imuran, and Prednisone in preventing rejections and prolonging graft survival in cadaver kidney transplantation, there is significant increase in the incidence of serious infections especially CMV infection in the Cellcept group. We recommend that these recipients should be monitored carefully with regard to early diagnosis and treatment of infections.

The problem of selecting antimicrobial agents before (or without) the results of susceptibility testing.

The appropriate selection of an antimicrobial regimen depends upon more factors than merely the results of susceptibility testing. It is a task more difficult today because of the recent development of many new antimicrobial agents. Clinicians who prescribe antibiotics need to invest time and energy beyond reading a package insert in order to gain familiarity with antimicrobial agents. Understanding the antimicrobial and pharmacologic properties of a few agents from each class of antimicrobial agents will help make the selection of empiric regimens less difficult. Essential to empiric therapy is frequent and habitual reassessment of antimicrobial regimens with possible application of cost-effective modifications kept in mind. Once the pathogen is isolated, the empiric regimen can be modified. The very last factor that is used in modification of the antimicrobial regimen is the result of susceptibility testing. Prior to (or without) this information, the clinical outcome of serious infections most often will depend upon the early institution of appropriate empiric therapy.